Inhalation aerosols are generally used for delivering medicament particles into the lungs, e.g. in the treatment of pulmonary asthma. It is necessary for successful medication that the particles be included in a sufficiently small size in inhalation air. However, it is generally known that only about 10% of a medicament dosage is capable of reaching its point of application in the lungs while most of it (about 80%) is retained in the upper respiratory tracts. The reasons for poor pulmonary penetration are known.
The inhalation aerosol consists of three main components: a medicament container, a metering valve mounted on the end thereof, and a plastic atomizer which contains a spray forming nozzle. During the course of dosage, a patient places the atomizer mouthpiece in his or her mouth, begins the oral inhalation and depressed the medicament container. Hence, the metering valve doses a certain volume of a propellant-medicament mixture which atomizes as a finely powdered spray into the mouth of a patient with some of the medicament finding its way into the lungs.
The only particles that can penetrate into the lungs in any significant degree are those whose diameter is 1-5 thousandths of a millimeter (microns). An inhalation aerosol spray only contains a small amount of such particles as most of the medicament is bound to considerably larger droplets formed by a non-volatile propellant; with one inhalation aerosol, the diameter of these droplets have been measured to be 43 microns at the moment of discharge.
The size of droplets is reduced as the volatilization of a propellant proceeds but, according to conducted studies, the volatilization of the largest droplets takes up to a couple of seconds. The non-volatile ingredients form a final particle, whose size is thus dependent on the size of a droplet issued from the nozzle as well as on the concentration of non-volatile ingredients therein.
When using an inhalation aerosol to measure a dose, the droplets arriving in the inhalation of a patient at a high speed mostly strike on the mucous membrane of the buccal cavity and a medicament contained therein does not reach the lungs. This portion of medicament is nearly inactive but, on the contrary, often leads to side effects. Also cold droplets may cause irritation. These negative effects can be mitigated by means of so-called inhalation chambers, wherein the medicament is sprayed prior to inhalation.
Studies have proved that nearly all inhalation aerosols produce particles too large for optimal pulmonary penetration. The problem is pronounced with medicaments having a relatively large single dose, the proportion of non-volatile ingredients being also large. Thus, it is obvious that by reducing the droplet size of a spray it is also possible to reduce the particle size and hence to improve the pulmonary penetration of a medicament. The volatilization or evaporation rate of small droplets is higher and their speed is reduced more rapidly as a result of air resistance. Such a spray is pleasant to a patient as the cold effect of a propellant is reduced.
Prior known factors having an effect on the droplet size include the pressure of a propellant and the diameter of a nozzle orifice (Polli, C.P., Grim, V.M., Bacher, F.A. and Yunker, M.H. (1969) J. Pharm. Sci. 58, 484-486) as well as the structure of a metering valve (Morch, F., (1978) Int. J. Pharm. 1, 213-218) and a nozzle (Pengilly, R.W. Keiner, J.A. J. Soc. Cosmet. Chem. (1977) 20:641-50). There is no published information dealing especially with the effect of the internal structure of a nozzle on the droplet and particle size of a spray.